| Size | Price | Stock | Qty |
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| 1mg |
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| 50mg | |||
| Other Sizes |
| Targets |
DDR-TRK-1 targets Discoidin Domain Receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase that plays important roles in cell proliferation, migration, and survival. DDR1 is implicated in various pathological processes including cancer progression, fibrosis, and tissue remodeling. DDR-TRK-1 exhibits an IC50 of 9.4 nM for DDR1 and binds to DDR1 with a Kd value of 4.7 nM. The compound is selective for DDR1 over DDR2 (IC50 = 188 nM) and Abl1 (IC50 >10,000 nM). DDR-TRK-1 also inhibits the TRK kinase family.
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| ln Vitro |
DDR-TRK-1 is a good candidate with an IC50 value of 9.4 nM relative to DDR1. DDR-TRK-1 also demonstrates reasonable pharmacokinetic (PK) characteristics. At an oral dosage of 20 mg/kg in rats, the oral bioavailability is 66.8% and the T1/2 value is 1.25 h. However, the area under the concentration-time curve (AUC) value of DDR-TRK-1 in mice was much larger than that in rats, showing that it has strong absorption properties in mice. The DDR1 inhibitory effect of DDR1-IN-3 was further validated by evaluating the binding affinity of DDR1-IN-3 to DDR1 protein. The results demonstrate that DDR-TRK-1 binds firmly to DDR1, with a binding constant (Kd) value of 4.7 nM[1].
In vitro, DDR-TRK-1 potently inhibits DDR1 kinase activity with an IC50 of 9.4 nM and binds to DDR1 with a Kd of 4.7 nM. The compound is significantly less potent against a panel of 400 non-mutated kinases, demonstrating excellent selectivity. DDR-TRK-1 inhibits colony formation and migration of Panc-1 pancreatic cancer cells, indicating its potential to suppress tumor cell aggressiveness. The compound also inhibits the TRK kinase family with IC50 values of 18-100 nM. The compound has a purity of ≥95%. |
| ln Vivo |
In a dose-dependent way, DDR-TRK-1 averts these pathogenic alterations brought on by BLM. The expression levels of fibrosis markers, such as fibronectin and α-smooth muscle actin (SMA), in lung tissue lysates are in agreement with these observations. Additional investigation revealed that the delivery of DDR-TRK-1 led to a dose-dependent reduction in the amount of hydroxyproline, a distinct amino acid present in collagen. All of the aforementioned information points to DDR-TRK-1's strong therapeutic potential for treating BLM-induced pulmonary fibrosis [1].
In vivo, DDR-TRK-1 has demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model. The compound's ability to inhibit DDR1, a key mediator of fibrosis and tissue remodeling, makes it a promising candidate for treating fibrotic diseases. Its selectivity for DDR1 over other kinases and its oral bioavailability support its potential as a therapeutic agent for fibrotic and oncological indications. |
| Enzyme Assay |
Receptor binding or kinase activity assays for DDR-TRK-1 are performed using purified recombinant DDR1 kinase domain. Kinase activity is measured by monitoring the phosphorylation of a peptide substrate in the presence of ATP. DDR-TRK-1 is incubated with the enzyme, substrate, and ATP at varying concentrations in appropriate kinase assay buffer. The reaction is stopped, and product formation is quantified using methods such as radiometric detection, fluorescence, or luminescence. IC50 values are calculated from concentration-response curves. Binding affinity (Kd) is determined using methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC).
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| Cell Assay |
Cellular assays for DDR-TRK-1 are performed using cancer cell lines that express DDR1, such as Panc-1 pancreatic cancer cells. Cells are cultured in appropriate media and treated with DDR-TRK-1 at varying concentrations for defined time periods. Cell viability and proliferation are assessed using standard assays such as MTT, CellTiter-Glo, or colony formation assays. Cell migration and invasion are assessed using wound healing or Boyden chamber assays. DDR1 signaling is assessed by measuring the phosphorylation of DDR1 and downstream signaling molecules by Western blot.
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| Animal Protocol |
In vivo studies with DDR-TRK-1 are conducted in mouse models of fibrosis or cancer, such as the bleomycin-induced mouse pulmonary fibrosis model. DDR-TRK-1 is administered via oral or intraperitoneal routes at defined doses and schedules. For fibrotic models, lung fibrosis is assessed by histological analysis, collagen content measurement, and assessment of lung function. For cancer models, tumor growth is monitored by caliper measurements. Pharmacokinetic parameters are determined from plasma samples collected at various time points.
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| ADME/Pharmacokinetics |
DDR-TRK-1 has a molecular weight of 492.50 and a molecular formula of C26H23F3N6O. The compound has demonstrated reasonable pharmacokinetic properties and promising oral therapeutic effects in preclinical models. The compound is soluble in DMSO. It should be stored at 2-8degC. As a selective DDR1 inhibitor with oral bioavailability, DDR-TRK-1 shows potential for further development as a therapeutic agent for fibrotic and oncological indications.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for DDR-TRK-1 are not extensively documented in publicly available sources. The compound is intended for research use only and is not approved for human therapeutic applications. In preclinical studies, DDR-TRK-1 has been administered in animal models without reported significant adverse effects at the doses used for efficacy evaluation. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and adherence to institutional biosafety guidelines.
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| References | |
| Additional Infomation |
DDR-TRK-1 is a selective inhibitor of Discoidin Domain Receptor 1 (DDR1) with an IC50 of 9.4 nM. It also inhibits the TRK family and is selective for DDR1 over DDR2 and Abl1. DDR-TRK-1 binds to DDR1 with a Kd of 4.7 nM and is significantly less potent against a panel of 400 non-mutated kinases. The compound has demonstrated reasonable pharmacokinetic properties and a promising oral therapeutic effect in a bleomycin-induced mouse pulmonary fibrosis model. DDR-TRK-1 is for research purposes only.
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| Molecular Formula |
C26H23F3N6O
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| Molecular Weight |
492.495635271072
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| Exact Mass |
492.188
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| CAS # |
1934246-19-1
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| PubChem CID |
121231414
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
36
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| Complexity |
763
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@H]1CN(CC2=C1C=CC(=C2)C(=O)NC3=CC(=CC(=C3)C(F)(F)F)N4C=C(N=C4)C)C5=CN=CN=C5
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| InChi Key |
CMJJZRAAQMUAFH-INIZCTEOSA-N
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| InChi Code |
InChI=1S/C26H23F3N6O/c1-16-11-34(23-9-30-14-31-10-23)13-19-5-18(3-4-24(16)19)25(36)33-21-6-20(26(27,28)29)7-22(8-21)35-12-17(2)32-15-35/h3-10,12,14-16H,11,13H2,1-2H3,(H,33,36)/t16-/m0/s1
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| Chemical Name |
(4R)-4-methyl-N-[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl]-2-pyrimidin-5-yl-3,4-dihydro-1H-isoquinoline-7-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0305 mL | 10.1523 mL | 20.3046 mL | |
| 5 mM | 0.4061 mL | 2.0305 mL | 4.0609 mL | |
| 10 mM | 0.2030 mL | 1.0152 mL | 2.0305 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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